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On the key role played by altered protein conformation in Parkinson’s disease
- Publication Year :
- 2008
-
Abstract
- On the basis of the previously proposed hierarchic organisation of the central nervous system (CNS) and of its syntropic behaviour, a view of neurodegenerative diseases focusing on the assemblage of abnormal multimeric proteins (pathologic protein mosaics (PMs)) is proposed. Thus, the main focus of the present paper is on Parkinson's disease (PD) as a neurodegenerative disease, which has as crucial feature protein conformational alterations and formation of pathological PMs. Two interconnected cellular dysfunctions are discussed as main pathogenic factors of PD syndromes, namely mitochondrial deficits (i.e. energy failure, especially critical for Substantia Nigra DA neurons) and conformational protein alterations (due to genetic or environmental causes). Conformational protein alterations can trigger pathological phenomena via the loss and/or the gain of new functions. In particular, altered proteins can lead to the formation of abnormal PMs, which can, inter alia, cause distortion of cellular structures, toxic functions and/or formation of improper membrane ion channels. In view of the fact that disordered proteins can easily acquire unwanted conformation, the "disorder index" (DI) for proteins involved in PD has been evaluated. It has been found that both alpha-synuclein and tau-protein have high DI. This datum is in agreement with the observation that these two proteins synergistically promote polymerisation of each other into amyloid fibrils, favouring the formation of Lewy bodies.
- Subjects :
- Energy failure
Disordered proteins
Parkinson's disease
Mitochondrial Diseases
Protein Conformation
Central nervous system
Substantia nigra
Nerve Tissue Proteins
tau Proteins
Disease
Biology
Hazardous Substances
Protein structure
medicine
Animals
Humans
Parkinson’s disease
Protein mosaics
Biological Psychiatry
Ion channel
Neurons
Brain
Parkinson Disease
Amyloid fibril
medicine.disease
Substantia Nigra
Psychiatry and Mental health
medicine.anatomical_structure
Neurology
alpha-Synuclein
Neurology (clinical)
Neuroscience
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....98a8aaee4ca56e5d899cb242db2f6eb1